What is Scleroderma and Primary Myocardial Disease?
Systemic sclerosis, or scleroderma, is a rare and complicated long-term disease that affects multiple body systems simultaneously. The word “scleroderma” comes from the ancient Greek words ‘skleros’, meaning hard, and ‘derma’, meaning skin. This name relates to one of scleroderma’s distinctive features – skin that becomes thick and hard.
Systemic sclerosis is marked by improper immune response causing inflammation, damage to blood vessels that results in physical and functional changes, and widespread scarring, or ‘fibrosis’, within organs and skin, which can result in damage to multiple organs in the body.
A particularly worrisome aspect of this disease is its effect on the heart, where it can affect the outer layer (pericardium), the heart muscle itself (myocardium), and the system responsible for regulating heart beats (conduction system). This heart disease occurs in both major forms of scleroderma: ‘diffuse’ and ‘limited’. However, it’s more common and usually more severe in the ‘diffuse’ form of the disease.
What Causes Scleroderma and Primary Myocardial Disease?
The exact cause and genetic links to systemic sclerosis, a disease affecting the body’s connective tissue, are not yet fully clear. There is a lot of belief though, that certain genetic factors and catch from the environment might cause this disease more frequently in people who are genetically inclined towards it. It has been observed that family members of those with systemic sclerosis are at a higher risk. However, twins do not always share the same chance of developing systemic sclerosis.
Likewise, research suggests that a particular cluster of genes, known as the major histocompatibility complex (MHC), plays a part in systemic sclerosis. There are certain alleles (different forms of the same gene) in the human leukocyte antigens (HLA) class II, which are connected to systemic sclerosis and the specific profile of antibodies in the system. For instance, the alleles HLA DQB1*0301, DRB1*1104, and DQA1*0501 have shown a strong connection to this disease.
There are other non-MHC genes also that have been linked to systemic sclerosis, like IRF5, STAT4, TNIP1, CD247, and PTPN22. Some of these genes have been implicated in other autoimmune diseases as well, like systemic lupus erythematosus, hinting towards the fact that imbalances in the immune system might be a crucial factor in the occurrence of systemic sclerosis.
Moreover, changes in the body’s chemistry involving DNA and proteins, which is termed as “epigenetic factors”, have been noticed in systemic sclerosis. These changes are believed to be triggered by environmental factors and mainly consist of changes in the structure of DNA, histones (proteins that pack DNA), and non-coding RNAs (RNA that doesn’t code for protein). As a result, there is an increase in genes promoting fibrosis (scarring), a fall in molecules that fight fibrosis, and an alteration in fibroblasts (cells producing collagen and other fibers). These changes have been associated with vascular diseases, fibrosis, B-cell activation, and antibody production.
Furthermore, certain infectious agents like viruses; cytomegalovirus (CMV), parvovirus B19, and Epstein-Barr virus (EBV), are thought to contribute to systemic sclerosis. Some theories propose that these viruses behave very much like the body’s own proteins, thereby confusing the immune system. Some of these viruses can also stimulate molecules promoting fibrosis in certain tissues. CMV, in particular, has been linked to vascular diseases, resulting in similar changes as systemic sclerosis. Likewise, being exposed to certain environmental factors, such as silica dust, occupational organic solvents, polyvinyl chloride, toluene, xylene, trichloroethylene, rapeseed oil, and L-tryptophan is being studied for their contribution towards systemic sclerosis.
Some drugs such as bleomycin, taxol, pentazocine, and cocaine have been linked to this disease as well. Finally, microchimerism, a peculiar condition where persistent fetal cells in the mother end up provoking an immune reaction, is believed by some to cause systemic sclerosis. However, this is not seen in all systemic sclerosis patients and is believed to be linked to certain genetic factors. Hence, the role of microchimerism in systemic sclerosis is still up for debate.
Risk Factors and Frequency for Scleroderma and Primary Myocardial Disease
Systemic sclerosis (SSc) is a condition that varies in how commonly it occurs in different studies. On average, there are about 8 to 56 new cases per million people every year, and about 38 to 341 people have the disease out of every million. This disease occurs more frequently in women, with the ratio of men to women being somewhere from 1 to 7 and it typically starts between the ages of 35 to 50. How the disease shows up can differ between men and women. For example, women usually get the disease at a younger age, have it for a longer time, and experience a milder form of the disease. However, women are more likely to have issues with their peripheral blood vessels and have a higher risk of lung-related complications, specifically high blood pressure in the lungs, which is the main cause of death.
Heart disease may be a problem for those who have both types of systemic sclerosis, yet it seems to be occur more often and more severely in those with the ‘diffuse’ type. Specific risk factors for developing heart disease when you have systemic sclerosis have been identified. These include having certain antibodies in your blood, rapid progression of skin thickening, and involvement of your skeletal muscles. Recent advances in heart assessments have shown that as many as 70% of people with systemic sclerosis may have heart complications, although most may not show obvious symptoms. However, it’s estimated that about 30% of those with the condition may have noticeable signs of heart complications.
Signs and Symptoms of Scleroderma and Primary Myocardial Disease
Microvascular coronary artery disease often doesn’t show any signs for years, and many people may not know they have it. Some people might experience chest pain similar to those who have a more common heart condition known as obstructive macrovascular coronary artery disease. Sometimes, signs of heart involvement might only be noticeable when undergoing advanced heart screening tests.
People with symptoms generally show signs of heart failure. These include constant tiredness, shortness of breath, and fluid accumulation. Sometimes, a specific condition known as acute myocarditis is also seen, particularly in people with another condition called overlap syndrome. This condition generally comes with abrupt heart failure signs and could sometimes also involve symptoms of another condition called skeletal myopathy, which includes muscle weakness and potential difficulty swallowing.
Signs of heart failure typically include:
- Difficulty in breathing, either while performing activities or at rest
- Breathing problems during sleep
- Constant fatigue
- Weight gain
- Swelling in lower extremities
- Elevated jugular vein pressure
- Third heart sound during heart examination
- Excessive blood flow in the liver.
In addition, individuals could also experience irregular heart rhythms, which usually come with symptoms such as rapid heartbeat, feeling like you might faint, or actual fainting.
Testing for Scleroderma and Primary Myocardial Disease
It’s important for people with scleroderma, a disease that causes hardening and tightening of the skin and connective tissues, to check for any heart disease. This is because usually, many of these patients don’t show early signs of heart problems. That’s why it’s been suggested that people with scleroderma, even without symptoms, should go through heart screenings regularly.
These screenings usually involve a general heart health check-up, which includes talking about your health history, a physical exam, an echocardiogram (a test that uses sound waves to create pictures of your heart), an electrocardiogram (a test that measures the electrical activity of your heartbeat), and lab testing for certain heart health indicators like troponin and plasma brain natriuretic peptide.
If a patient is experiencing symptoms, more tests might be recommended. This can include a cardiac magnetic resonance imaging (a type of scan that gives detailed images of your heart), stress testing (tests that measure how your heart reacts when you’re physically exerted), and/or cardiac catheterization (a test to check blood flow in your coronary arteries and heart). If the results from these tests are concerning, a referral to a cardiologist (a doctor who specializes in heart diseases) may be necessary.
When managing scleroderma, it is recommended for both rheumatologists (doctors who specialize in rheumatic diseases like scleroderma) and cardiologists to work together. This ensures you receive complete and comprehensive care, and the most appropriate and efficient treatment recommendations.
Treatment Options for Scleroderma and Primary Myocardial Disease
Generally, the treatment for Systemic Sclerosis (SSc), a disease that involves the hardening and tightening of your skin and connective tissues, focuses mainly on managing the specific organs affected by this condition.
First, we’ll talk about the treatment of a condition called microvascular coronary artery disease. This refers to a condition where the small blood vessels that supply your heart with blood don’t work as they should. The treatment resembles the standard approach we would take with anyone, and includes improving symptoms like chest pain with specific drugs like antivirulence medications that stop platelets from sticking together and forming clots, lipid-lowering therapy that reduces the level of fats in your blood, nitrates that widen (dilate) your blood vessels, and calcium channel blockers that can slow the heart rate and relax the blood vessels.
Heart failure, a condition that compromises the heart’s function to pump blood adequately, is managed similarly in SSc patients as in the general population. Non-selective beta blockers, a type of drugs which can reduce blood pressure and slow the heart rate, should usually be used due to their lower risk of worsening the disease’s actions in the body. There’s limited evidence that vasodilators, drugs that open up blood vessels, such as calcium channel blockers or angiotensin-converting enzyme inhibitors (which relax arteries and veins) might have some benefits on heart function and blood flow in people with SSc.
Heart failure treatment will depend on the type of heart failure. In SSc patients diastolic heart failure is more common, which means their hearts can’t relax and fill properly. The main treatment options are diuretics (or water pills) and controlling blood pressure. For systolic heart failure, which means the heart can’t pump blood forward as it should, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) are among the main treatment options. There might also be a need for diuresis (increased fluid elimination), and possibly even the use of medications that boost the heart’s ability to pump blood and special devices in certain cases. Medical conditions that can worsen heart diseases, such as hypertension, diabetes, and high lipid levels, should be kept under control.
In the case of myocardial inflammation (when your heart’s muscle layers become inflamed) due to SSc, treatment options are fewer and less certain. This is because the number of studies testing certain treatments is limited and observational in nature. However, treatment options such as systemic steroids, cyclophosphamide, mycophenolate, and intravenous immunoglobulin (which help to modulate the immune system) have been suggested, and have shown some success in some cases.
What else can Scleroderma and Primary Myocardial Disease be?
There are a number of health conditions that can be mistaken for Systemic Sclerosis (SSc). These include:
- Scleredema: This condition is marked by an abundance of mucin causing the skin to thicken. It usually affects the upper back and the back part of the neck, making the skin feel hard and “woody”. Scleredema is often associated with diabetes, viral infections, and a type of disease called monoclonal gammopathies.
- Scleromyxedema: This is another condition that can look like SSc. It typically presents with rashes and hard skin, similar to scleroderma, along with mucin deposits. Furthermore, this condition is connected to monoclonal gammopathy, but not thyroid disease.
- Eosinophilic Fasciitis: This can also mimic SSc. In this case, the connective tissue under the skin becomes thick due to collagen build-up.
- Morphea: This condition is often mistaken for SSc, causing skin to thicken. However, Morphea is a generally milder, inflammatory disorder that needs to be considered when diagnosing.
Additionally, heart disease seems to be common in people with SSc, even if they don’t show any symptoms. Therefore, doctors need to consider other causes of heart disease if the symptoms don’t align with typical signs of SSc.
What to expect with Scleroderma and Primary Myocardial Disease
When the heart muscle (myocardium) is affected in Systemic Sclerosis (SSc), a group of diseases that result in hard, thickened areas of skin, it often predicts a poor outcome. Multiple studies have confirmed that a significant number of deaths in SSc cases are linked to heart problems, such as heart failure and irregular heartbeats (arrhythmias).
In fact, heart disease ranks as the third most common cause of death in SSc patients, following lung issues caused by scarring in the lung tissue (Interstitial lung disease) and high blood pressure in the lungs (pulmonary arterial hypertension). A certain type of study known as a meta-analysis showed that, in those with heart disease, the risk of death was 2.8 times higher compared to those without heart disease.
This underlines the significance of early detection and management of heart disease in individuals with SSc.
Possible Complications When Diagnosed with Scleroderma and Primary Myocardial Disease
Heart problems linked to SSc, or systemic sclerosis, usually increase the risk of death. The issues that can happen due to myocardial disease (heart muscle disease) include heart failure, problems with heart rhythm regulation, and abnormally rapid heart rhythms.
- Increased risk of death due to heart conditions related to SSc
- Heart failure due to myocardial disease
- Rhythm regulation problems in the heart
- Abnormally rapid heart rhythms
Preventing Scleroderma and Primary Myocardial Disease
People living with scleroderma need to be made aware of their condition and informed about how to detect potential heart issues. Some signs to watch out for may include new chest pain, difficulty breathing, rapid heartbeats, unexpected weight gain, and constant tiredness. If a person with scleroderma also has heart failure, they need to be especially aware of symptoms and signs of “volume overload,” which means their body has more blood and fluid than it should.
